美国纽约唐纳德和芭芭拉·祖克医学院Steven Fishbane研究组取得一项新突破。他们发现Difelikefalin可治疗血液透析患者的瘙痒症。这一研究成果发表在2019年11月8日出版的《新英格兰医学杂志》上。

Difelikefalin是一种外周限制性和选择性的kappa阿片受体激动剂，被认为可改善慢性肾病患者的瘙痒症状。

在这项双盲、安慰剂对照的临床3期试验中，研究组随机分配接受血液透析的中重度瘙痒患者，在12周内每周接受三次静脉滴注Difelikefalin或安慰剂。采用24小时最大瘙痒强度数字评分量表（WI-NRS）对瘙痒程度进行评分，0-10分，分数越高，瘙痒强度越大。

共有378名患者接受了随机分组。Difelikefalin组中51.9%的患者WI-NRS评分比基线至少下降3分，而安慰剂组仅有30.9%。Difelikefalin组中WI-NRS评分至少下降3分患者的估算百分比为49.1%，显著高于安慰剂组（27.9%）。根据5-D瘙痒量表和皮肤指数-10量表，治疗12周时，与基线相比，Difelikefalin组患者的瘙痒相关生活质量得以显著改善。12周时，Difelikefalin组中WI-NRS评分至少下降4分患者的估算百分比为37.1%，显著高于安慰剂组（17.9%）。但Difelikefalin组的患者更易发生腹泻、头晕和呕吐等不良反应。

总之，与安慰剂相比，Difelikefalin可显著降低透析患者的瘙痒强度，且提高瘙痒相关的生活质量。

附：英文原文

Title: A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus

Author: Steven Fishbane, M.D., Aamir Jamal, M.D., Catherine Munera, Ph.D., Warren Wen, Ph.D., Frédérique Menzaghi, Ph.D.

Issue&Volume: 2019-11-08

Abstract:

Background

Difelikefalin is a peripherally restricted and selective agonist of kappa opioid receptors that are considered to be important in modulating pruritus in conditions such as chronic kidney disease.

Methods

In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned patients undergoing hemodialysis who had moderate-to-severe pruritus to receive either intravenous difelikefalin (at a dose of 0.5 μg per kilogram of body weight) or placebo three times per week for 12 weeks. The primary outcome was the percentage of patients with an improvement (decrease) of at least 3 points from baseline at week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS; scores range from 0 to 10, with higher scores indicating greater itch intensity). The secondary outcomes included the change from baseline in itch-related quality-of-life measures, the percentage of patients with an improvement of at least 4 points in the WI-NRS score at week 12, and safety.

Results

A total of 378 patients underwent randomization. A total of 82 of 158 patients (51.9%) in the difelikefalin group had a decrease of at least 3 points in the WI-NRS score (primary outcome), as compared with 51 of 165 (30.9%) in the placebo group. The imputed percentage of patients with a decrease of at least 3 points in the WI-NRS score was 49.1% in the difelikefalin group, as compared with 27.9% in the placebo group (P<0.001). Difelikefalin also resulted in a significant improvement from baseline to week 12 in itch-related quality of life as measured by the 5-D itch scale and the Skindex-10 scale. The imputed percentage of patients with a decrease of at least 4 points in the WI-NRS score at week 12 was significantly greater in the difelikefalin group than in the placebo group (37.1% [observed data: 64 of 158 patients] vs. 17.9% [observed data: 35 of 165 patients], P<0.001). Diarrhea, dizziness, and vomiting were more common in the difelikefalin group than in the placebo group.

Conclusions

Patients treated with difelikefalin had a significant reduction in itch intensity and improved itch-related quality of life as compared with those who received placebo.

DOI: 10.1056/NEJMoa1912770

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1912770